Postmenopausal women who reported a panic attack were three times more likely to have a heart attack or stroke over the next five years, according to results of a cohort study reported in the October issue of the Archives of General Psychiatry. They also had nearly twice the risk of all-cause mortality than other women.

These associations remained after controlling for depression and other cardiovascular risk factors, found Jordan W. Smoller, M.D., Sc.D., of Massachusetts General Hospital here, and colleagues.

The findings suggest these women represent a group "in whom careful monitoring and cardiovascular risk reduction may be particularly important," they said.

The study also "adds panic attacks to the list of emotional states and psychiatric symptoms that have been linked to excess risk of cardiovascular disease and death in nonclinical samples," they wrote.

Large-scale prospective studies, including the Women's Health Initiative study, have shown increased risk of heart disease with depression. Phobic anxiety, anger, hostility, and chronic worry have also been associated with cardiovascular outcomes.

To see whether the same was true for panic attacks, Dr. Smoller's group analyzed responses of 3,369 community-dwelling postmenopausal women to a questionnaire about panic attacks completed at their enrollment into the broader Myocardial Ischemia and Migraine Study. The study was conducted at 10 of the 40 centers participating in the Women's Health Initiative study.

Among them, 9.7% reported having had at least one full-blown panic attack -- defined as an attack of sudden fear, anxiety, or extreme discomfort accompanied by four or more cognitive or autonomic symptoms from a 12-symptom checklist -- in the six months prior to baseline.

Another 8.1% reported a limited-symptom panic attack with one to three rather than at least four symptoms.

The combined end point of coronary heart disease and stroke (HR 3.08, 95% CI 1.60 to 5.94).

All-cause mortality (HR 1.75, 95% CI 1.04 to 2.94).

Excluding the 149 women with a history of cardiovascular disease yielded similar hazard ratios (3.5 for coronary heart disease, 95% CI 1.29 to 9.54; 2.77 for heart disease and stroke, 95% CI 1.37 to 5.59, and 1.98 for all-cause mortality, 95% CI 1.15 to 3.41).

Limited-symptom panic attacks were associated with a nonsignificant doubling in risk of the combined endpoint of coronary heart disease and stroke (HR 2.05, 95% CI 0.99 to 4.23), but none of the endpoints together or separately were significant compared with women without panic attacks. However the number of women reporting these attacks was small, raising the possibility of a type II error.

But, controlling for panic attacks, depression was not a significant factor for all-cause mortality (HR 1.08, 95% CI 0.61 to 1.94) or for the combined endpoint of coronary heart disease and stroke (HR 0.89, 95% CI 0.39 to 2.03).

However, further study is needed to determine whether the connection between panic attacks and cardiovascular events and death is causal, they said.

Anxiety itself can have adverse cardiovascular effects, such as coronary ischemia, heightened platelet activation and altered hemodynamic reactivity, they noted. Or, the panic attacks reported by women who developed cardiovascular outcomes could have actually been episodes of ischemia or arrhythmia, they said.

A limitation of the study noted by the authors was "that our panic attack questionnaire was a cross-sectional measure assessing the presence of at least one panic episode during a six-month period. Thus, we cannot distinguish cardiovascular outcomes among women who may have had multiple recurrent attacks (or who may have met criteria for panic disorder) from those who may have had infrequent or sporadic attacks."

The Women's Health Initiative program was funded by the National Heart, Lung, and Blood Institute. The Myocardial Ischemia and Migraine Study was funded by GlaxoSmithKline.

Dr. Smoller reported potential conflicts of interest for Hoffman-La Roche, Roche Diagnostics, and Eli Lilly. Other researchers disclosed financial relationships with a range of pharmaceutical companies and other organizations. One researcher reported receiving a grant from GlaxoSmithKline for this study.

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine

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